1. Field of the Invention
The present invention relates to a cell culture support for forming string-shaped beating cardiomyocyte aggregates and a method for forming string-shaped cardiomyocyte aggregates with the use of the same.
2. Background Art
A method whereby somatic stem cells (tissue stem cells) represented by myelocytes are selected and transplanted (injected) directly into the heart of a patient, has been studied as a method for cardiomyocyte transplantation and myocardial regenerative therapy. In addition, there have been studies regarding the induction of efficient differentiation of ES cells (embryonic stem cells) of non-human mammals into cardiomyocytes. In recent years, there have also been studies regarding the efficient induction of differentiation of tissue stem cells (e.g., undifferentiated cells contained in fatty tissue) into cardiomyocytes. Thus, the range of cells that are used as sources for cardiomyocyte transplantation and myocardial regenerative therapy has been expanding. However, a technique for artificially constructing tissue having functions of the myocardium, such as the function of beating, has not yet been established.
A variety of cell culture supports for forming a sheet-type cell aggregate used for regenerative medicine and the like have been available (e.g., JP Patent Publication (Kokai) No. 2004-170935 A, JP Patent Publication (Kokai) No. 2005-168494 A, and JP Patent Publication (Kokoku) No. 6-104061 B (1994)). However, cardiomyocyte sheets produced by the above techniques do not have the function of beating. In the case of a cardiomyocyte sheet prepared with the use of a conventional cell culture support comprising primary cardiomyocytes (cells released from connective tissue (collected from a baby rat) by collagenase treatment), cardiomyocytes account for half of cells dispersed therein, and vascular endothelial cells, fibroblast cells, and the like account for the other half thereof. A single cardiomyocyte that serves as a pacemaker cell can be found in approximately 10,000 cardiomyocytes. Cells are electrically connected to each other via a gap junction on a cardiomyocyte sheet formed in a random manner. In such case, when cells are connected to each other, the pathway for beating is established in a manner such that electric signals generated from a plurality of pacemaker cells are transmitted through cardiomyocytes and the other cells. In the case of a sheet comprising confluent cells, synchronization takes place via the shortest pathway including pacemaker cells. However, in such case, electric signal emission lacks direction. Thus, during beating, the entire sheet repeatedly dilates and contracts; however such dilation and contraction lack direction.